PROJECT SUMMARY For decades, the mouse has been the premier animal model for studies of human disease, providing the opportunity to explore experimental questions that are intractable for direct study in humans. As a result, key insights have been obtained for a variety of clinical conditions. Spurred by advances in technology and international efforts to systematically knock out all of the protein coding genes in the genome, the number of genetically engineered mice has expanded rapidly in the past 20 years. The responsibility for maintenance and distribution of mutant mice was initially placed on individual investigators, which was a tremendous burden in terms of cost, labor and space. In 1999, the NIH recognized the need for a resource to protect the investment in mutant mouse strains and ensure open access to all biomedical researchers and established the Mutant Mouse Regional Resource Centers (MMRRC). Since 1999, the central goal of the MMRRC-UNC has been to work collectively with MMRRC consortium partners to develop and maintain high standards for importation, rederivation, cryopreservation, and distribution of mutant mouse strains to biomedical investigators. The MMRRC- UNC will continue to contribute to the goals of the Consortium in the next project period by implementing the following Specific Aims devoted to continuing its successful role as a cryoarchive and distribution center and incorporating research goals that synergize with and extend the value of the resource: 1) Streamline and improve operating procedures to increase importation, distribution, and cryoarchive of mouse strains. 2) Establish, maintain, and distribute a comprehensive cryoarchive for the Collaborative Cross (CC) resource. 3) Develop and disseminate computational tools for mouse genetic QC and genomics research, which will enhance phenotypic reproducibility. 4) Investigate the interaction of genetics and environment on experimental variability and reproducibility. !